Transcript Sepsis Self

Continuing Education Credit
Date of Release: 6/15/2015
Date of Expiration: 6/14/2016
Estimated time to complete this educational activity: 1 hour
Continuing Education Credit
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Statement of Need
Sepsis kills more than 210,000 Americans each year
and is becoming more common, especially in the hospital.
Sepsis is a medical emergency that can be difficult to define,
diagnose, and treat, but every minute counts in the effort
to save lives. This learning activity will describe how bedside
analyte testing could aid therapeutic decision making
and improve the prognosis for patients with sepsis.
Intended Audience
The primary audience for this learning activity are health care
professionals (physicians and nurses) who are involved
in the testing, diagnosis, treatment, and management of sepsis
and are interested in the role of biomarkers to improve the care
for these patients.
Learning Objectives
After completing this activity, the participant should be able to:
1. Review the epidemiology of sepsis.
2. Describe biomarkers used in the diagnosis
and treatment of sepsis.
3. Explain how to evaluate sepsis tests and results.
4. Identify the benefits of point-of-care analyte testing
in sepsis patients.
Medical Advisement
We would like to acknowledge the following medical experts
who served as advisors to this educational program:
Emanuel P. Rivers, MD, MPH
Thomas Ahrens, DNS, RN, PhD
Arthur P. Wheeler, MD
Jill A. Sellers, BSPharm, PharmD
Disclosures
Thomas Ahrens, DNS, RN, PhD
No financial relationships to disclose.
Emanuel P. Rivers, MD, MPH
No financial relationships to disclose.
Jill A. Sellers, BSPharm, PharmD
No financial relationships to disclose.
Arthur P. Wheeler, MD
No financial relationships to disclose.
Introduction to Sepsis
Definition, Etiology, Morbidity and Mortality
Sepsis
“Hectic fever, at its inception, is difficult to recognize
but easy to treat; left unattended it becomes easy
to recognize and difficult to treat.”
~ Niccolo Machiavelli
The Prince (1513)
Definition of Sepsis
• Sepsis
– Systemic response to infection
– Manifested by two or more SIRS criteria
as a result of proven or suspected infection
• Temperature ≥ 38C or ≤ 36C
• HR ≥ 90 beats/min
• Respirations ≥ 20/min
• WBC count ≥ 12,000/mm3 or ≤ 4,000/mm3
or > 10% bands
• PaCO2 < 32 mmHg
ACCP/SCCM Consensus Conference. Crit Care Med. 1992;20(6):864-74.
Case Study
Case Study: Mr. Z
• Mr. Z is a 47 year-old male who was admitted to
the emergency department. He is complaining of
a toothache that has been present for 7 days.
• His tooth pain is severe and he came
to the emergency department since
he could not see his dentist until the
morning. He has drainage from tooth #20,
for which a culture has been obtained
and sent to the lab.
• He tells you “My tooth is killing me! You can pull it if
you need to. I feel like it is going to explode.”
Case Study: Mr. Z
• Mr. Z is alert and oriented.
• He has a history of hypertension and had a hemorrhagic
stroke 10 years ago but has had no major health issues
since this time.
• His heart and lung sounds are normal
and his skin is cool and moist. He has
good capillary refill, abdomen soft and
non-tender.
• He is currently on Cefoxitin (Mefoxin) 2 g IV q6h.
Case Study: Mr. Z
Admission
Heart Rate
111
Temperature
38.7
SPO2
0.96
NIBP
128/88 (101)
Respiratory Rate
22
SPO2: Pulse oximetry oxygen saturation;
NIBP: Non-invasive blood pressure
Questions
1) Does Mr. Z have signs of sepsis?
Yes
2) What is a blood test that would be useful?
Lactate
Case Study: Mr. Z
Admission
Heart Rate
Temperature
SPO2
NIBP
Respiratory Rate
Serum Lactate
111
38.7
0.96
128/88 (101)
22
3.5
After 20 mL/kg normal saline
(10 minutes)
Heart Rate
104
Temperature
38.6
SPO2
0.96
NIBP
130/88 (102)
Respiratory Rate
22
Case Study: Mr. Z
After 4 Hours
Heart Rate
88
Temperature
38.1
SPO2
0.98
NIBP
133/78 (94)
Respiratory Rate
17
Serum Lactate
1.8
• A decrease in lactate shows improved perfusion.
• If the lactate had remained elevated, more fluids could
have been given.
• The use of the lactate allowed the clinician to better evaluate
the seriousness of the situation.
• Often, vital signs are normal when lactates are elevated.
Sepsis is Serious.
• Sepsis is a serious medical condition caused by an
overwhelming immune response to infection.
• Complex chain of events:
– Inflammatory and anti-inflammatory processes
– Humoral and cellular reactions
– Circulatory abnormalities
• Results in impaired blood flow, which damages organs
by depriving them of nutrients and oxygen.
http://www.nigms.nih.gov/Education/factsheet_sepsis.htm
The Intracellular Immune Response to Infection
Adapted from Holmes CL, Russell JA, Walley KR. Chest. 2003;124:1103-15.
Symptoms of Sepsis
• Sepsis can begin in different parts of the body
and can have many different symptoms.
• Rapid breathing and a change in mental status,
may be the first signs of sepsis.
• Other symptoms include:
– Fever
– Chills/hypothermia
– Decreased urination
– Tachycardia
– Nausea and vomiting
The Sepsis Continuum
Infection/Trauma
Local or systemic infection
or traumatic injury
SIRS
A clinical response arising from
a nonspecific insult, including
≥ 2 of the following:
Sepsis
SIRS with a presumed
or confirmed infection
• Temperature > 38ºC or < 36ºC
• Heart rate > 90 beats/min
• Respiratory rate > 20 breaths/min
or PaCO2 < 32 Torr
• WBC > 12,000 cells/mm3,
< 4,000 cells/mm3, or
> 10% immature
Severe
Sepsis
Sepsis with ≥ 1 sign of
organ failure:
• Cardiovascular
(refractory hypotension)
• Renal
• Respiratory
• Hepatic
• Hematologic
• CNS
• Unexplained metabolic
acidosis
Adapted from Bone RC, Balk RA, Cerra FB et al. Chest. 1992;101:1644-55.
The Relationship Between SIRS, Sepsis,
and Severe Sepsis
Other
Sepsis
Pancreatitis
Infection
Severe
Sepsis
SIRS
Trauma
Burns
Bone RC, Balk RA, Cerra FB et al. Chest. 1992;101:1644-55.
Locations for Common Infection
Lungs
Skin and
soft tissue
Vascular Catheters
(endovascular)
Abdomen
Appendix
http://www.nigms.nih.gov/Education/factsheet_sepsis.htm
Urinary Tract
Microbes
• Many different types of microbes can cause sepsis:
– Bacteria (most common)
– Fungi
– Viruses
• Severe cases often result from a localized infection
but sepsis can also spread throughout the body.
Staphylococcus sp. (Bacteria)
CDC/ Matthew J. Arduino
Aspergillus sp. (Fungi)
CDC/ Robert Simmons
http://www.nigms.nih.gov/Education/factsheet_sepsis.htm
Influenza (Virus)
CDC/ Erskine. L. Palmer, PhD;
M. L. Martin
Mortality Rates
• Sepsis remains the leading cause of death
in critically ill patients in the United States.
• Each year 750,000 people will develop sepsis.
Deaths Per Year
250,000
200,000
150,000
100,000
50,000
0
AIDS
Breast
Cancer
Severe
Sepsis
National Center for Health Statistics, 2001.
American Cancer Society, 2001.
Angus DC, Linde-Zwirble WT, Lidicker J et al. Crit Care Med. 2001;29(7):1303-10.
Sepsis Incidence
Rate per 10,000 Population
50
Hospitalizations with septicemia or sepsis
Hospitalizations for septicemia or sepsis
40
30
20
10
0
2000
2001
2002
2003
2004
2005
Year
CDC/NCHS, National Hospital Discharge Survey. 2000-2008.
2006
2007
2008
Sepsis Hospitalization by Gender
Rate per 10,000 Population
300
Male
Female
250
200
150
100
0
All Ages
< 65
65-74
Ages in Years
CDC/NCHS, National Hospital Discharge Survey. 2000-2008.
75-84
> 85
Sepsis Incidence by Race
Population-Adjusted Incidence
of Sepsis (No./100,000)
500
Other
Black
White
400
300
200
100
0
1979 1981 1983 1985 1987 1989 1991 1993 1995 1997 1999 2001
Martin GS, Mannino DM, Eaton S et al. N Engl J Med. 2003;348:1546-54.
Sepsis Incidence in the United States: 2000
Incidence per 100,000
250
200
150
100
50
0
Sepsis
Breast
Cancer
Acute
Multiple
Myocardial Sclerosis
Infarction
Lung
Cancer
Colon
Cancer
AIDS
Martin GS, Mannino DM, Eaton S et al. N Engl J Med. 2003;348:1546-54.
SEER Cancer Statistics Review. National Cancer Institute. http://progressreport.cancer.gov/2007
HIV/AIDS Surveillance Report. Centers for Disease Control. 2001;11.
Incidence & Prevalence: 2006 Chart Book on Cardiovascular and Lung Diseases. NHLBI, NIH. 2006.
Turabelidze G. J Neurol Sci. 2008;269:158-62.
Sepsis Length of Stay
Length of Stay (Days)
10
Septicemia or Sepsis
Other hospitalizations
8
6
4
2
0
All Ages
< 65
Ages in Years
CDC/NCHS, National Hospital Discharge Survey. 2000-2008.
> 65
Sepsis Morbidity and Mortality
• In severe cases, one or more organs fail.
• Worst case scenario:
–
–
–
–
Blood pressure drops
Septic shock
Multiple organ system failure
Death
• The number of sepsis cases per year has been on the rise:
– Aging population, the increased longevity of people
with chronic diseases, the spread of antibiotic-resistant
organisms, an upsurge in invasive procedures and broader
use of immunosuppressive and chemotherapeutic agents.
http://www.nigms.nih.gov/Education/factsheet_sepsis.htm
Sepsis Mortality
Mortality Rate1
Sepsis
10-20%
Severe sepsis
20-50%
Septic shock
40-80%
• Mortality rates increase by 10% for every hour
without antibiotics.2
• Survivors show continued impaired quality of life
after 2 years.3
1Martin
GS. Expert Rev Anti Infect Ther. 2012;10:701-6.
A, Roberts D, Wood KE, et al. Crit Care Med. 2006;34(6):89–1596.
3Winters BD, Eberlein M, Leung J et al. Crit Care Med. 2010;38(5):1276-83
2Kumar
Financial Implications
• Annual care for hospital patients with severe sepsis
averaged approximately $14 billion in 2008.1
Billion ($)
• Some facilities spend as much as $24 billion annually.2
16
14
12
10
8
6
4
2
0
1997
1HCUP
2Lagu
2002
2008
Facts and Figures, 2006: Statistics on Hospital-Based Care in the United States. Rockville (MD)2008.
T, Rothberg MB, Shieh MS et al. Crit Care Med. 2012 Mar;40(3):754-61.
Sepsis Biomarkers
Use in Diagnosis, Risk, and Response
Diagnosis of Sepsis
• Bacteria in the blood or other body fluids
– Source of the infection
– A high or low white blood cell count
– A low platelet count
– Low blood pressure
– Too much acid in the blood (acidosis)
– Altered kidney or liver function
• Biomarkers
Sepsis Biomarkers: Screening
• Diagnosis of sepsis and evaluation of its severity
is complicated by the highly variable and non-specific
nature of signs and symptoms.
• Distinguishing patients with localized infections
or SIRS from those with sepsis is challenging.
• SIRS is not specific to sepsis and can result
from other conditions such as acute pancreatitis
and immunodeficiencies.
• Biomarkers of sepsis may improve diagnosis
and therapeutic decision making.
Lever A, Mackenzie I. Br Med J. 2007;335:879–83.
Sepsis Biomarkers
• More than 170 biomarkers have been
assessed for sepsis prognosis and diagnosis.
• Some common biomarkers include:
– Procalcitonin (PCT)
– Interleukins and other cytokines
– C-reactive protein (CRP)
– sCD163
– Serum lactate
– sTREM
Pierrakos C, Vincent JL. Crit Care. 2010,14:R15.
Procalcitonin and C-Reactive Protein
Procalcitonin
Release of PCT into the bloodstream depends on sepsis severity.
Dropping PCT levels indicate increased survival rates.
Persistent elevated PCT is predictive for an unfavorable outcome.
More favorable kinetic profile than other markers: levels increase
4-12 hours after onset of infection.
C-Reactive Protein
Can also be elevated in non-sepsis conditions.
Both pro and anti-inflammatory effects.
Secretion starts 4 hours after infection and peaks at 36 hours.
Used to diagnose multiple infections.
Ability to discriminate patients with and without sepsis is moderate.
May be able to stratify risk early (day 1) but not as effective as other
markers such as PCT or sTREM-1.
Bloos F & Reinhart K. Virulence. 2014;5:154-60.
Serum Lactate and Interleukins
Interleukin-62
Serum Lactate
Most widely used biomarker for organ dysfunction.
1 Faix
2
Systemic inflammation and infection increases lactate levels.
Intermediate to high serum lactate levels indicate increased risk.
Reference ranges for serum lactate levels may be too high for sepsis.
Most goal-directed resuscitation is based on initial lactate levels and
clearance.
Appears rapidly and reaches peak levels within 2 hours.
May have similar discriminating power to PCT.
Levels related to severity and outcomes in sepsis patients.
Levels decrease with controlled infection.
Lack of large-scale studies to determine clinical value.
J. Crit Rev Clin Lab Sci. 2013;50:23-36.
Bloos F & Reinhart K. Virulence. 2014;5:154-60.
sCD163 and sTREM-1
sCD163
Increases seen at the beginning of infection.
Applicable in early sepsis diagnosis.
Independent risk factor for sepsis survival.
Prognostic in sepsis and SIRS.
Lack of large-scale studies to determine clinical value.
sTREM-12
Upregulated after exposure to bacteria or fungi.
Non-survivors of sepsis have higher levels than survivors.
Sensitivity and specificity similar to PCT.
Is elevated in other inflammatory conditions.
Lack of large-scale studies to determine clinical value.
1 Su
2
L, Feng L, Song Q et al. Mediators Inflamm. 2013;2013:969875.
Bloos F & Reinhart K. Virulence. 2014;5:154-60.
Laboratory Assays for Sepsis
Assay
Measurement
Lactate*
(mg/dl)
Septic shock
(n = 2)
Uncomplicated sepsis
(n = 19)
No Sepsis
(n = 45)
P-Value
2.8
1.7 (1.40–2.20)
1.1 (0.73–1.55)
0.06
MRproADM (nmol/l)
1.05 (1.05–1.05)
0.91 (0.55–1.26)
0.82 (0.52–1.18)
0.78
MRproANP
(pmol/l)
201 (102–300)
178 (91.6–232)
143 (77.2–349)
0.98
PCT
(ng/ml)
0.34 (0.26–0.43)
0.32 (0.19–1.17)
0.18 (0.07–0.54)
0.04
Copeptin
(pmol/l)
13.4 (13.1–13.7)
13.2 (6.29–34.1)
17.1 (8.2–34.8)
0.61
proET-1
(pmol/l)
118 (104–132)
75 (36.9–111)
80 (51.5–106)
0.53
All values are expressed as median (interquartile range) or % (number) accordingly.
MRproADM, midregional proadrenomedullin; MRproANP, proatrial natriuretic peptide; PCT, procalcitonin;
proET-1, proendothelin-1.
* Only available in 14 patients (septic shock = 1, uncomplicated sepsis = 7, no sepsis = 4).
Hicks CW, Engineer R, Benoit JL et al. Eur J Emerg Med. 2014;21:112-7.
PCT ROC Curve for Final Diagnosis of Sepsis
1.0
0.9
True Positive
Sensitivity
0.8
0.7
0.6
0.5
AUC = 0.67
0.4
0.3
0.2
0.1
0.0
0.0
0.2
0.4
0.6
0.8
1.0
1=Specificity
False Positive
Adapted from Hicks CW, Engineer R, Benoit JL et al. Eur J Emerg Med. 2014;21:112-7.
Procalcitonin Reference Range
Normal subjects
< 0.5 pg/ml
Chronic inflammatory processes
and autoimmune diseases
< 0.5 pg/ml
Viral infections
< 0.5 pg/ml
Mild to moderate localized
bacterial infections
< 0.5 pg/ml
SIRS, multiple trauma, burns
Severe bacterial infections, sepsis,
multiple organ failure
0.5 – 2 pg/ml
> 2 pg/ml
(often 10 – 100 pg/ml)
ACCP/ Society of Critical Care Medicine Consensus Conference. Crit Care Med. 1992;20:864-74.
Harbarth S, Holeckova K, Froidevaux C et al. Am J Respir Crit Care Med. 2001;164:396-402.
Christ-Crain M, Jaccard-Stolz D, Bingisser R et al. Lancet. 2004;363:600-7.
Survival Curves in Severe Sepsis and
Septic Shock: Baseline Cortisol and Post-ACTH
Basal Plasma Cortisol Level  34 g/dL,  max > 9 g/dL
Probability of Survival
1.00
0.80
Basal Plasma Cortisol Level  34 g/dL,  max  9 g/dL or
Basal Plasma Cortisol Level > 34 g/dL,  max > 9 g/dL
0.60
0.40
0.20
Basal Plasma Cortisol Level > 34 g/dL,  max  9 g/dL
0
0
7
14
21
Time (Days)
Annane D, Sebille V, Troche G et al. J Am Med Assoc. 2000;283:1038-45.
28
CRP Levels Correlate With Mortality
and Organ Failure in Sepsis
30
CRP Day 0
CRP Day 2
*
30
Survivors
Non-Survivors
p = 0.001
p = 0.002
CRP mg/dL
CRP mg/dL
* p < 0.05
20
10
0
0
1
2
(116/115) (111/110) (56/56)
3
>4
(20/19)
(4/4)
Number of Organ Failures
Lobo SM, Lobo FR, Bota DP et al. Chest. 2003;123:2043-9.
20
10
0
Day 0
Day 2
Survivors vs. Non-Survivors
Lactic Acidosis
Anaerobic Glycolysis
Aerobic Glycolysis
(Cytoplasm)
(Mitochondria)
O2
Glycogen
Glucose
Pyruvate
Citric
Acid
Cycle
CO2
H2O
Lactate
1 Glu + 2 ADP + 2 Pi
1 Glu + 6 O2 + 38 ADP + 38 Pi
2 Lactate + 2 ATP
6 CO2 + 6 H20 + 38 ATP
Mizock BA, Falk JL. Crit Care Med. 1992;20:80-95.
Diagnostic and Therapeutic Markers
80
60-80% Normal
60
40
50% Lactic Acidosis
(≥ 4 mmol/L)
SvO2
Serum Lactate as a Predictor of Mortality
50
28%
25
20
15
10
5
0
0-2.4
2.5-3.9
> 4.0
28 day in-hospital mortality
2 Shapiro
38-40%
40
30
20
10.0
0.0
Lactate1
1 Trzeciak
% of Mortality Rate
% of Mortality Rate
30
0-2.4
2.5-3.9
> 4.0
N = 827
N = 238
N = 112
Initial Lactate (mmol/L)2
Death within 3 days
S, Dellinger RP, Chansky ME et al. Intensive Care Med. 2007;33:970-7.
NI, Howell MD, Talmor D et al. Ann Emerg Med. 2005; 45:524-8.
Serum Lactate as a Predictor of Mortality
Mean Lactate Level (mmol/L)
7
Non-survival
Survival
6
5
p = 0.001
4
p < 0.001
3
2
1
0
Arrival Scene (T1)
Emergency
Department (T2)
Jansen TC, van Bommel J, Mulder PG et al. Crit Care. 2008,12:R160.
Value of Blood Lactate Levels
First Lactate
Measurement
N = 124
< 3.5 mmol/l
11 Missing
(0 Died)
Second Lactate
Measurement
8/66
(12%)
Mortality
≥ 3.5 mmol/l
p < 0.001
24/58
(41%)
Mortality
7 Missing
(4 Died)
N = 55
< 3.5 mmol/l
8/54
(15%)
Mortality
N = 51
≥ 3.5 mmol/l
< 3.5 mmol/l
0/1
(0%)
Mortality
2/14
(14%)
Mortality
p = 1.00
18/37
(49%)
Mortality
p = 0.025
N = 106
Second Lactate
Cumulative
≥ 3.5 mmol/l
< 3.5 mmol/l
10/68
(15%)
Mortality
≥ 3.5 mmol/l
p < 0.001
18/38
(47%)
Mortality
Adapted from Jansen TC, van Bommel J, Mulder PG et al. Crit Care. 2008,12:R160.
Lactate, SBP, and Mortality
60
Mortality (%)
50
40
30
20
10
0
> 3.5
< 100
SBP (mmHg)
> 100
< 3.5
Jansen TC, van Bommel J, Mulder PG et al. Crit Care. 2008,12:R160.
Lactate (mmol/l)
Serum Lactate and Mortality in Severe Sepsis
• Initial serum lactate
• High initial serum
lactate associated with
↑ mortality regardless
of presence of shock
or MODS.
45
28-Day Mortality (%)
evaluated in 839 adults
admitted with severe
sepsis.
p = 0.001
50
40
35
p = 0.022
p < 0.001
30
25
20
p = 0.024
15
10
5
0
Low Int High
Low Int High
Non-Shock
Shock
Mikkelsen ME, Miltiades AN, Gaieski DF et al. Crit Care Med. 2009;37:1670-7.
Improving Lactate a Good Prognostic Sign
Lactate (mmol/L)
8
6
p < 0.05
Non-survivors
p < 0.05
4
p < 0.01
Survivors
2
0
INITIAL +8h
+16h
+24h
Time
Bakker J, Gris P, Coffernils M et al. Am J Surg. 1996;171:221-6.
FINAL
Sepsis Testing and Results
Guidelines, Algorithms, and Protocols
Factors to Consider When Evaluating Sepsis
• Blood gases
• Electrolytes
• Glucose
• Hematocrit
• Lactate
Sepsis Resuscitation Bundle
The Sepsis Resuscitation Bundle is published by
the Surviving Sepsis Campaign and is used by multiple
hospitals across the country.
The goal is to perform all indicated tasks 100% of the time
within the first 6 hours of identification of severe sepsis.
Surviving Sepsis Campaign. http://sccm.org
Within 6 Hours
Within 3 Hours
Sepsis Resuscitation Bundle
1. Measure serum lactate.
2. Obtain blood cultures prior to antibiotics (best within 45 minutes).
3. Administer a broad-spectrum antibiotic, within 1 hour if possible.
4. In the event of hypotension deliver an initial minimum
of 30 mL/kg of crystalloid or an equivalent.
5.
Apply vasopressors for hypotension not responding to initial fluid
resuscitation to maintain mean arterial pressure (MAP) > 65 mmHg.
6.
In the event of persistent hypotension despite fluid resuscitation
(septic shock) and/or lactate > 4 mmol/L:
a. Achieve a central venous pressure (CVP) of 8-12 mmHg.
b. Achieve a central venous oxygen saturation (ScvO2) > 70% or mixed
venous oxygen saturation (SvO2) > 65%.
7.
Re-measure serum lactate.
Surviving Sepsis Campaign. http://sccm.org
Sepsis Management Bundle
Efforts to accomplish these goals should begin immediately, but these
items may be completed within 24 hours of presentation for patients
with severe sepsis or septic shock.
The tasks are:
1. Administer low-dose steroids for septic shock in accordance
with a standardized ICU policy. If not administered, document
why the patient did not qualify for low-dose steroids based upon
the standardized protocol.
2. Administer recombinant human activated protein C (rhAPC) in accordance
with a standardized ICU policy. If not administered, document why the
patient did not qualify for rhAPC.
3. Maintain glucose control > 70 mg/dL, but < 150 mg/dL.
4. Maintain a median inspiratory plateau pressure (IPP) < 30 cm H2O for
mechanically ventilated patients.
Surviving Sepsis Campaign. http://sccm.org
Polymerase Chain Reaction
• Polymerase chain reaction (PCR)-based
assays facilitate the detection of pathogens
in the blood in a few hours.
• Benefits
– Correlates with blood cultures
– Acceptable rate of false-positives
– Higher diagnostic sensitivity
– Shorter evaluation time leads to earlier diagnosis
Wellinghausen N, Kochem AJ, Disque C et al. J Clin Microbiol. 2009; 47(9): 2759-65.
Point-of-Care Analyte Benefits
• A 2010 study published in the Journal of Emergency Medicine
found that point-of-care testing provided a reliable and feasible
way to measure serum lactate at the bedside.1
• Base excess (BE)
– Some studies suggest BE is an accurate marker for the
prediction of elevated lactate in the emergency department (ED).2
– Some studies also show poor correlation due to effects
of other conditions.3
• Point-of-care lactate is useful in the diagnosis of sepsis
at the bedside
– Recommended for institutions where clinical decisions are limited
by lack of laboratory infrastructure or reliability.4
1
Shapiro NI, Fisher C, Donnino M et al. J Emerg Med. 2010;39:89-94.
Montassier E, Batard E, Segard J et al. Am J Emerg Med. 2010. Epub ahead of print.
3 Martin MJ, FitzSullivan E, Salim A et al. Am J Surg. 2006;191:625-30.
4 Moore CC, Jacob ST, Pinkerton R et al. Clin Infect Dis. 2008;46:215-22.
2
Point-of-Care Analyte Testing
• Single-use, self-calibrating, 100-150 uL WB sample
• pH, pCO2, pO2, Na, K, iCa, Glu, Hct (plus calculated
values TCO2, HCO3, BE, sO2, Hb)
• Analytes on a single test card
• Requires only room temperature storage*
• Bar-coded for patient safety
– Cant use expired cards*
– Smart card technology
• Low-cost test cards
– < $ than benchtop systems
*unique market features
Turnaround Time
• Serum lactate must be available
with rapid turnaround time (within minutes)
to effectively treat severely septic patients.
• An arterial blood gas analyzer located
in the clinical laboratories usually
accomplishes this.
• Hospitals should invest in adequate
equipment in to meet present standards
of care for septic patients.
• If a central analyzer is not efficient
in a particular hospital setting, point-of-care
analyzers should be evaluated for faster
turnaround time.
http://www.survivingsepsis.org/bundles
www.emcrit.org/wp-content/uploads/lactate-faq.pdf
Time and Cost for Measuring Blood Lactate
Chiron
Accusport®
Central
Laboratory
Time of transportation
(min)
--
--
9.6 ± 3.8
Time for results (min)
1
1
85 ± 35
1-10
1
45-168
Electrodes: 4 x $134
Total: $536
Device: $156
--
--
Test strip: $1.22
Quality Control
Bottle: $11.10
--
Costs for 197 samples
$536
$248
$493
Costs of transportation
of one sample
--
--
$3.61
Time for results (range)
Hardware
Reagents
Boldt J, Kumle B, Suttner S et al. Acta Anaesthesiol Scand. 2001;45:194–9.
2012 Guideline Updates
• Two sets of blood cultures drawn prior to antimicrobial therapy
and give antimicrobials within 1 hour of diagnosis.
• One set of culture drawn percutaneously and one set drawn
through each vascular access device, unless if the device
was inserted within 48 hours.
• If the blood culture drawn from the vascular access device turns
positive ≥ 2 hours before the peripheral blood culture, data supports
that the vascular access device is the source of the infection.
• Initial empiric broad spectrum antimicrobial therapy (selected
to cover all suspected organisms) within 1 hour after recognition
of septic shock and severe sepsis without septic shock.
• Mortality rises every hour without antimicrobials.
Dellinger RP, Levy MM, Rhodes A et al. Crit Care Med. 2013;41(2):580-637.
2012 Guideline Updates
• Antimicrobial regiment should be reassessed daily for de‐escalation.
Empiric combination therapy should not be administered for > 3‐5 days.
De-escalate to most appropriate single therapy pending susceptibility
as soon as possible.
• If invasive candidiasis suspected, send 1,3 beta‐D‐glucan assay (2D),
mannan and anti‐mannan antibody assay (2C).
• Suspect viral, start antiviral. Test for seasonal variations.
• Use procalcitonin level or other markers to consider discontinuation of e
mpiric antibiotic for those who was initially diagnosed septic, but have no
subsequent evidence of infection.
• Duration of therapy typically 7‐10 days.
• No antimicrobial therapy if patient’s severe inflammatory state is not due
to infectious causes.
Dellinger RP, Levy MM, Rhodes A et al. Crit Care Med. 2013;41(2):580-637.
CCF Sepsis Flowchart
SIRS + Suspected Infection
SIRS 2 Criteria
• T > 38° or < 36°
• HR > 90
• RR > 20 or PaCO2 32 mmHg
• WBC > 12 K or < 4 K; Bands > 10%
Identification
Lactate POC (< 15’)
Fluid Bolus
Organic Dysfunction
SBP < 90 p bolus
Lactate > 4
No
Sepsis
Yes
Rapid
CV
Abs
Severe Sepsis/
Septic Shock
Labs
Cultures
Mechanical
Ventilation
Initiate Sepsis
Bundle
Central Venous Arterial
Line Access (< 2°)
CVP < 8
Preload
NS 500 cc IVB until CVP > 8
CVP > 15 + MAP > 110
NTG 10-60 mcg/min until
CVP < 12 or MAP < 110
MAP < 65
Norepinephrine 2-20 mcg/min or
Dopamine 5-20 mcg/kg/min
MAP > 110
NTG 10-60 mcg/min until MAP < 90
or Hydralazine 10-40 mg IV
EGDT
Afterload
Central
Venous Oxygen
Content
ScvO2 < 70%
Hgb
ScvO2
No
Bundled Therapies
Antibiotics
(< 4°)
Goals
Achieved
?
Hgb < 10
ScvO2 < 70%
• CVP 8-12
• MAP 65-110
• ScvO2 > 70%
• Lactate improved
APACHE III
> 25
Activated
Protein C
Rivers EP. N Engl J Med. 2001;345:1368-77.
Glycemia
Control
80-110
Semirecumbent
Position
Transfuse PRBC
Dobutamine 2.5-20 mcg/kg/min
Risk Stratification
• APACHE II1
• Mortality in Emergency Department Score
(MEDS)2-3
• Procalcitonin-based algorithms4
• BC sepsis guidelines algorithm5
1 Giamarellos-Bourboulis
EJ, Norrby-Teglund A, Mylona V et al. Crit Care. 2012;16:R149.
E. Em Med Pract. 2011;11(5).
3Hermans MAW, Leffers P, Jansen LM et al. Emerg Med J. 2012;29:295-300.
4 Kopterides P, Siempos II, Tsangaris I et al. Crit Care Med. 2010;38(11):2229-41.
5 Sepsis Guide. BC Sepsis Network. www.bcpsqc.ca Accessed 03/22/14.
2 Booker
Protocols Reduce Mortality
• Sepsis protocols improve clinical
outcomes and mortality rates
• Sepsis Bundle
• Hospital-specific protocols
– Sepsis guideline based
– Early goal directed therapy
– Rapid delivery of antibiotics
Surviving Sepsis Campaign. http://sccm.org
Talmor D, Greenberg D, Howell MD et al. Crit Care Med. 2008;36(4):1168-74.
Sepsis
Identification, Treatment, and Outcomes
Identification of Sepsis
Are any two of the following SIRS criteria present and new to the patient?
Heart rate > 90 beats/min
Respiratory rate > 20/min
Temperature < 36.0 or > 38.3C
Acutely altered mental state
Blood glucose > 7.7 mmol/L (in absence of diabetes)
White cell count < 4 or > 12 x 109/L
If YES, patient has SIRS
Is there a clinical suspicion of new infection?
Cough/sputum/chest pain
Dysuria
Abdominal pain/distension/diarrhea
Headache with neck stiffness
Line infection
Cellulitis/wound/joint infection
Endocarditis
If YES, patient has Sepsis
Is there evidence of any organ dysfunction?
Systolic BP < 90/mean < 65 mmHg
Urine output < 0.5 mL/kg/h for 2 h
Lactate > 2 mmol/L after initial fluids
Creatinine > 177 umol/L
INR > 1.5 or aPTT > 60 s
Platelets < 100 x 109/L
Bilirubin > 34 umol/L
SpO2 > 90% unless O2 given
If YES, patient has Severe Sepsis
Daniels R. J Antimicrob Chemother. 2011;66(Suppl 2):ii11–ii23.
Treatment of Sepsis
• Early goal-directed therapy: standard operating
procedure
– Apply with critical care/sepsis team if patient remains hypotensive
or lactate remains high following fluid challenges
1. Site central venous catheter using ultrasound guidance where
practicable, according to proper procedures for infection control
2. If central venous pressure (CVP) < 8 mmHg, give further fluid
challenges to achieve a target CVP of > 8 mmHg (> 12 mmHg
if ventilated) unless the patient shows signs of fluid overload
3. If patient remains hypotensive, start a norepinephrine infusion
to target SBP > 90 mmHg or MBP > 65 mmHg.
Daniels R. J Antimicrob Chemother. 2011;66(Suppl 2):ii11–ii23.
Sepsis Outcomes
• Lactate clearance is associated with improved patient outcome.
• Lactate measurement is associated with increased risk of death
independent of other aspects of sepsis bundle guidelines.
• Point-of-care measurements of lactate are faster than
central laboratories.
– May be beneficial for serial measurements.
Nguyen HB, Rivers EP, Knoblich BP et al. Crit Care Med. 2004;32(8):1637-42.
Afessa B, Keegan MT, Schramm GE et al. Crit Care Med. 2011;15(Suppl 1): P286.
Boldt J, Kumle B, Suttner S et al. Acta Anaesthesiol Scand. 2001;45:194–9.
Conclusion